Molecular Genotype in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency in Hungarian Population 74

Abstract

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a result of mutations in the CYP21B gene encoding steroid 21-hydroxylase enzyme(21-OH). To detect mutations of CYP21B gene in 141 Hungarian patients, we isolated DNA from whole blood and analyzed by allele specific PCR. The classical salt-losing (SL) form was diagnosed in 90 index cases, the classical non-salt-losing (NSL) form in 39 and the late-onset (LO) form in 12 patients. We detected deletion and the seven most common mutations. Percentage distribution of abnormalites was as follows: Deletion 9.85%, I2splice 41.9%, I173N 17.25%, V282L 8.09%, Q319stop 6.69%, R357W 7.04%, L308insT 4.92% and Cluster E6 0.35%. In 32 cases (11.26%) we were not able to determine the mutation. In conclusion, the splice site mutation in intron 2 (the G mutation in the position of 659) was found to be the most frequent mutation in 21-OHD. This study confirms genotype - phenotype association.